@article{0f8f1e9af1114a7cb7ca2731076f4382,
title = "Impact of apolipoprotein ε4-cerebrospinal fluid beta-amyloid interaction on hippocampal volume loss over 1 year in mild cognitive impairment",
abstract = "Background: The majority of studies relating amyloid pathology with brain volumes have been cross-sectional. Apolipoprotein ε4 (APOE ε4), a genetic risk factor for Alzheimer's disease, is also known to be associated with hippocampal volume loss. No studies have considered the effects of amyloid pathology and APOE ε4 together on longitudinal volume loss. Methods: We evaluated whether an abnormal level of cerebrospinal fluid beta-amyloid (CSF Aβ) and APOE ε4 carrier status were independently associated with greater hippocampal volume loss over 1 year. We then assessed whether APOE ε4 status and CSF Aβ acted synergistically, testing the significance of an interaction term in the regression analysis. We included 297 participants: 77 cognitively normal, 144 with mild cognitive impairment (MCI), and 76 with Alzheimer's disease. Results: An abnormal CSF Aβ level was found to be associated with greater hippocampal volume loss over 1 year in each group. APOE ε4 was associated with hippocampal volume loss only in the cognitively normal and MCI groups. APOE ε4 carriers with abnormal CSF Aβ in the MCI group acted synergistically to produce disproportionately greater volume loss than noncarriers. Conclusion: Baseline CSF Aβ predicts progression of hippocampal volume loss. APOE ε4 carrier status amplifies the degree of neurodegeneration in MCI. Understanding the effect of interactions between genetic risk and amyloid pathology will be important in clinical trials and our understanding of the disease process.",
keywords = "Apolipoprotein E4, Beta-amyloid, Biomarker, Hippocampal atrophy, MRI",
author = "Chiang, {Gloria C.} and Insel, {Philip S.} and Duygu Tosun and Norbert Schuff and Diana Truran-Sacrey and Raptentsetsang, {Sky T.} and Thompson, {Paul M.} and Reiman, {Eric M.} and Jack, {Clifford R.} and Fox, {Nick C.} and Jagust, {William J.} and Harvey, {Danielle J.} and Beckett, {Laurel A.} and Anthony Gamst and Aisen, {Paul S.} and Petersen, {Ron C.} and Weiner, {Michael W.}",
note = "Funding Information: Dr. Fox also receives funding from the Medical Research Council, the Alzheimer{\textquoteright}s Research Trust (ART) , and the National Institute for Health Research . Funding Information: Dr. Weiner serves on scientific advisory boards for Bayer Schering Pharma, Eli Lilly, Nestle, CoMentis, Neurochem, Eisai, Avid, Aegis, Genentech, Allergan, Lippincott, Bristol Meyers Squibb, Forest, Pfizer, McKinsey, Mitsubishi, and Novartis. He has received non–industry-supported funding for travel; serves on the editorial board of Alzheimer{\textquoteright}s & Dementia; received honoraria from the Rotman Research Institute and BOLT International; receives research support from Merck & Co, Avid, NIH (U01AG024904 [PI], P41 RR023953 [PI], R01 AG10897 [PI], P01AG19724 [Coinvestigator], P50AG23501[Coinvestigator], R24 RR021992 [Coinvestigator], R01 NS031966 [Coinvestigator], and P01AG012435 [Coinvestigator]), the Department of Defense (DAMD17-01-1-0764 [PI]), and the Veterans Administration (MIRECC VISN 21 [Core PI]); and holds stock in Synarc and Elan Pharmaceuticals. Funding Information: Dr. Jack is an investigator in clinical trials sponsored by Pfizer; serves as a consultant for Elan Pharmaceuticals; and receives research support from the NIH ( R01-AG11378 ) and the Alexander Family Alzheimer{\textquoteright}s Disease Research Professorship of the Mayo Foundation . Funding Information: This work was funded by the National Institutes of Health (NIH) , NIBIB ( T32 EB001631-05 ). Funding Information: This research was also supported by NIH grants P30 AG010129, K01 AG030514 , and the Dana Foundation. Funding Information: The participants in this study were recruited through the ADNI between 2005 and 2008, a longitudinal study including 56 centers in the United States and Canada was conducted with the purpose of identifying biomarkers of early AD for clinical trials ( www.adni-info.org ). The ADNI was funded by the National Institute on Aging (NIA), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), the Food and Drug Administration, private pharmaceutical companies, and nonprofit organizations, as a 5-year public–private partnership. Funding Information: Dr. Fox has served on the scientific advisory boards of Alzheimer{\textquoteright}s Research Forum, Alzheimer{\textquoteright}s Society, and ART, and editorial boards of Alzheimer{\textquoteright}s Disease and Associated Disorders, Neurodegenerative Diseases, and BioMed Central: Alzheimer{\textquoteright}s Research and Therapy. He holds a patent for QA Box that may accrue revenue. In the last 5 years, his research group has received payment for consultancy or for conducting studies from Abbott Laboratories, Elan Pharmaceuticals, Eisai, Eli Lilly, GE Healthcare, IXICO, Lundbeck, Pfizer Inc, Sanofi-Aventis, and Wyeth Pharmaceuticals. He receives research support from the Medical Research Council ( G0801306 [PI], G0601846 [PI] ), NIH ( U01 AG024904 [Co-investigator {sub contract}]), ART (ART/RF/2007/1 [PI]), and the National Institute for Health Research (as a Senior Investigator). ",
year = "2011",
month = sep,
doi = "10.1016/j.jalz.2010.12.010",
language = "English (US)",
volume = "7",
pages = "514--520",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "5",
}